Platinum Chemotherapy Plus Paclitaxel With Bevacizumab and Atezolizumab in Metastatic Carcinoma of the Cervix
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|ClinicalTrials.gov Identifier: NCT03556839|
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : December 3, 2019
The study will integrate the efficacy of combining the anti programmed death-ligand 1 (anti-PD-L1) agent atezolizumab with the current standard of care in Stage IVB , persistent or recurrent carcinoma of the cervix, namely cisplatin/paclitaxel/bevacizumab. It will be explored the combination of bevacizumab plus atezolizumab, with no patient selection based on PD-L1 expression, allowing an all-comer assessment of atezolizumab activity.
The study is a randomized open label phase III trial to investigate the impact of atezolizumab in combination with bevacizumab and cisplatin/paclitaxel chemotherapy on overall survival and will employ the intent to treat principle, and random assignment to one of the 2 arms will be balanced according to disease histology (squamous versus adenocarcinoma), prior platinum therapy as a radiation sensitizer (no prior cis-Radiotherapy (RT) versus prior cis-RT) and chemotherapy backbone (cisplatin versus carboplatin).
This trial will be run in an open label design due to the following considerations: the control arm is the standard of care for women diagnosed with metastatic, persistant or recurrent cervical cancer because of its impact on overall survival and the primary endpoint of the study is overall survival (OS), so blinding is not needed to ensure a robust assessment.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma of the Cervix, Stage IVB||Drug: Atezolizumab Drug: Bevacizumab Drug: Cisplatin Drug: Paclitaxel||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||404 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase III Trial of Platinum Chemotherapy Plus Paclitaxel With Bevacizumab and Atezolizumab Versus Platinum Chemotherapy Plus Paclitaxel and Bevacizumab in Metastatic (Stage IVB), Persistent, or Recurrent Carcinoma of the Cervix|
|Actual Study Start Date :||September 25, 2018|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||December 2023|
Active Comparator: Arm A
Cisplatin 50mg/m2 + paclitaxel 175mg/m2+ bevacizumab 15mg/kg i.v D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologic therapy, namely bevacizumab, upon investigator discussion.
Other Name: Avastin
Experimental: Arm B
cisplatin 50mg/m2 + paclitaxel 175mg/m2 + bevacizumab 15mg/kg + atezolizumab 1200mg i.v, D1 Q3W.Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologics therapy, namely bevacizumab plus atezolizumab, upon investigator discussion.
Other Name: Tecentriq
Other Name: Avastin
- Overall survival [ Time Frame: 48 months ]Time from the date of randomization to the date of death due to any cause
- Progression-free survival [ Time Frame: 48 months ]Time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
- Objective Response Rate [ Time Frame: 48 months ]Based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
- Duration of response [ Time Frame: 48 months ]Based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
- Incidence of Treatment-Emergent Adverse Events of combining atezolizumab to chemotherapy plus bevacizumab compared to cisplatin/paclitaxel (CP) plus bevacizumab. [ Time Frame: 48 months ]Incidence, nature and severity of adverse events (AEs) assessed by CTCAE version 4.03
- First subsequent therapy [ Time Frame: 48 months ]Time from randomization to first subsequent therapy or death due to any cause
- Progression-free survival 2 [ Time Frame: 48 months ]Time from randomization to the second event of disease progression per radiological criteria, start of a new line of therapy, due to symptomatic deterioration or to death due to any cause
- Patient-reported outcomes (PROs) of function and health related quality of life (HR-QOL) associated with atezolizumab + CP + bevacizumab compared to bevacizumab + CP alone, as measured by the functional and GHS/ HRQoL scales of EORTC QLQ-C30 [ Time Frame: 48 months ]Mean and mean changes from baseline score in patient function (role, physical) and GHS/HRQoL, by assessment timepoint and between treatment arms, as assessed by the functional and GHS/HRQoL scales of EORTC QLQ-C30.
- Pharmacokinetics (PK) of atezolizumab [ Time Frame: 36 months ]Serum concentration (Cmin) of atezolizumab
- Pharmacokinetics (PK) of atezolizumab [ Time Frame: 36 months ]Serum concentration (Cmax) of atezolizumab
- Incidence of anti-therapeutic antibodies (ATAs) [ Time Frame: 36 months ]Incidence of ATAs during the study relative to the prevalence of ATAs at baseline
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03556839
|Contact: Javier Sanchez López, MBA MSc||+34 669 528 firstname.lastname@example.org|
|Contact: Carmen Marqués, MDemail@example.com|
|Principal Investigator:||Ana Oaknin, MD PhD||Vall d´Hebron University Hospital|